The globus pallidus (GP) communicates with widespread cortical areas that support various functions, including motivation, cognition and action. Anatomical tract-tracing studies revealed that the anteroventral GP communicates with the medial prefrontal and orbitofrontal cortices, which are involved in motivational control; the anterodorsal GP communicates with the lateral prefrontal cortex, which is involved in cognitive control; and the posterior GP communicates with the frontal motor cortex, which is involved in action control. This organization suggests that distinct subdivisions within the GP play specific roles. Neurophysiological studies examining GP neurons in monkeys during behavior revealed that the types of information coding performed within these subdivisions differ greatly. The anteroventral GP is characterized by activities related to motivation, such as reward seeking and aversive avoidance; the anterodorsal GP is characterized by activity that reflects cognition, such as goal decision and action selection; and the posterior GP is characterized by activity associated with action preparation and execution. Pathophysiological studies have shown that GABA-related substances or GP lesions result in abnormal activity in the GP, which causes site-specific behavioral and motor symptoms. The present review article discusses the anatomical organization, physiology and pathophysiology of the three major GP territories in nonhuman primates and humans.

Figure 6: Neuronal population activities for positive motivational context-preferring (upper panel) and negative motivational context-preferring neurons (lower panel) in the VP for conditioned stimulus (CS)-related activity and anticipatory activity. Monkeys performed different motivational tasks in which they chose approach or avoidance behaviors to obtain a reward or prevent the delivery of an air puff depending on the motivational context (Saga et al., 2016). The blue histogram (mean ± SEM) indicates neuronal activity in trials in the positive motivational context and red represents activity in trials in the negative motivational context. Each panel is aligned with CS onset, touch screen and unconditioned stimulus (US) delivery and the gray zone represents the time period of the behavioral event. Data modified from Saga et al. (2016) used with permission from Oxford University Press.

Mentions:
In a specific Pavlovian conditioning task, neurons in the GPi and GPe responded to the appearance of a visual stimulus that was associated with either reward (juice) or aversion (air puff to the face) as well as to the delivery of the outcome (reward or air puff, Joshua et al., 2009). Thus, the GP is involved in processing not only appetitive signals but aversive signals as well. We further investigated this phenomenon as monkeys performed a behavioral task and found that the VP is involved in negatively as well as positively motivated behavior (Saga et al., 2016). In that particular task, a conditioned stimulus (CS) predicted either an appetitive outcome (a drop of juice) or an aversive outcome (air puff) and the monkeys were required to choose between approaching or avoiding the cue by performing a reaching movement. Usually, the monkeys made an approach behavior in the appetitive context and an avoidance behavior in the aversive context. These context dependent behaviors indicate that the CSs provide the information concerning motivational context. Accordingly, the VP neurons of these monkeys discriminated between the appetitive and aversive contexts (or between positive and negative motivations) by exhibiting excitatory and inhibitory activity modulation during the presentation of the CS (Figures 5F, 6). Additionally, the VP neurons showed anticipatory activity in advance of the delivery of the outcome. In another study, excessive activation of the VP caused by microinjections of bicuculline (a GABAA antagonist) resulted in decreased avoidance behavior in the aversive context, as well as the premature termination of a trial (Saga et al., 2016). Interestingly, this effect was observed exclusively in the aversive motivational context, which suggests that excessive activation of the VP increases sensitivity to aversive contexts. Excessive activation of the VP is known to result in repetitive licking and biting of the fingers (Grabli et al., 2004), which is a behavioral hallmark of anxiety or stress. Thus, these results indicate that VP plays a crucial role in the performance of behaviors in the aversive as well as appetitive context.

Figure 6: Neuronal population activities for positive motivational context-preferring (upper panel) and negative motivational context-preferring neurons (lower panel) in the VP for conditioned stimulus (CS)-related activity and anticipatory activity. Monkeys performed different motivational tasks in which they chose approach or avoidance behaviors to obtain a reward or prevent the delivery of an air puff depending on the motivational context (Saga et al., 2016). The blue histogram (mean ± SEM) indicates neuronal activity in trials in the positive motivational context and red represents activity in trials in the negative motivational context. Each panel is aligned with CS onset, touch screen and unconditioned stimulus (US) delivery and the gray zone represents the time period of the behavioral event. Data modified from Saga et al. (2016) used with permission from Oxford University Press.

Mentions:
In a specific Pavlovian conditioning task, neurons in the GPi and GPe responded to the appearance of a visual stimulus that was associated with either reward (juice) or aversion (air puff to the face) as well as to the delivery of the outcome (reward or air puff, Joshua et al., 2009). Thus, the GP is involved in processing not only appetitive signals but aversive signals as well. We further investigated this phenomenon as monkeys performed a behavioral task and found that the VP is involved in negatively as well as positively motivated behavior (Saga et al., 2016). In that particular task, a conditioned stimulus (CS) predicted either an appetitive outcome (a drop of juice) or an aversive outcome (air puff) and the monkeys were required to choose between approaching or avoiding the cue by performing a reaching movement. Usually, the monkeys made an approach behavior in the appetitive context and an avoidance behavior in the aversive context. These context dependent behaviors indicate that the CSs provide the information concerning motivational context. Accordingly, the VP neurons of these monkeys discriminated between the appetitive and aversive contexts (or between positive and negative motivations) by exhibiting excitatory and inhibitory activity modulation during the presentation of the CS (Figures 5F, 6). Additionally, the VP neurons showed anticipatory activity in advance of the delivery of the outcome. In another study, excessive activation of the VP caused by microinjections of bicuculline (a GABAA antagonist) resulted in decreased avoidance behavior in the aversive context, as well as the premature termination of a trial (Saga et al., 2016). Interestingly, this effect was observed exclusively in the aversive motivational context, which suggests that excessive activation of the VP increases sensitivity to aversive contexts. Excessive activation of the VP is known to result in repetitive licking and biting of the fingers (Grabli et al., 2004), which is a behavioral hallmark of anxiety or stress. Thus, these results indicate that VP plays a crucial role in the performance of behaviors in the aversive as well as appetitive context.

The globus pallidus (GP) communicates with widespread cortical areas that support various functions, including motivation, cognition and action. Anatomical tract-tracing studies revealed that the anteroventral GP communicates with the medial prefrontal and orbitofrontal cortices, which are involved in motivational control; the anterodorsal GP communicates with the lateral prefrontal cortex, which is involved in cognitive control; and the posterior GP communicates with the frontal motor cortex, which is involved in action control. This organization suggests that distinct subdivisions within the GP play specific roles. Neurophysiological studies examining GP neurons in monkeys during behavior revealed that the types of information coding performed within these subdivisions differ greatly. The anteroventral GP is characterized by activities related to motivation, such as reward seeking and aversive avoidance; the anterodorsal GP is characterized by activity that reflects cognition, such as goal decision and action selection; and the posterior GP is characterized by activity associated with action preparation and execution. Pathophysiological studies have shown that GABA-related substances or GP lesions result in abnormal activity in the GP, which causes site-specific behavioral and motor symptoms. The present review article discusses the anatomical organization, physiology and pathophysiology of the three major GP territories in nonhuman primates and humans.